Figure 7. eIF2Bα PNDM mutations may lead to inadequate stress sensing and ISR in pancreatic β cells.

eIF2Bα missense mutations that lead to PNDM are present in residues which interact with eIF2 or the binding surface of p-eIF2α. Additionally, yeast studies have found that specific PNDM mutations can also disrupt eIF2B bodies and impact eIF2B decameric formation. This suggests that p-eIF2α binding to eIF2B is impeded, indicating a hindrance in stress-sensing which may lead to pancreatic β cell dysfunction or reduced number.